The adult respiratory distress syndrome (ARDS) has been linked pathogenically to the activation of complement and complement-mediated neutrophil deposition in the lung. We have described a series of 20 patients with profound neutropenia who developed the clinical syndrome of ARDS after developing sepsis or septic shock. Pathologic studies obtained on half of these patients revealed classic pulmonary pathology for ARDS with no neutrophils present in the lung and with no evidence of an infectious pneumonitis. This study indicates that the ARDS syndrom can occur in the absence of neutrophils. Other pathogenic mechanisms without neutrophils must also be able to result in ARDS. These studies assessing mechanisms of ARDS are the first step toward designing novel therapeutic interventions to reverse the currently dreadful prognosis.